ENST00000371837.5:c.62-33490C>T

Variant names:

• chr10-89261888-G-A
• rs7922193
• NM_001440836.1:c.132-14239C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371837.5(LIPA):​c.62-33490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,958 control chromosomes in the GnomAD database, including 15,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15925 hom., cov: 32)
• Consequence: LIPA ENST00000371837.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 5 publications found

Genes affected

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

LIPA Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• cholesteryl ester storage disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Wolman disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371837.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	NM_001440836.1		c.132-14239C>T		intron	N/A	NP_001427765.1
	LIPA	NM_001440838.1		c.15-14239C>T		intron	N/A	NP_001427767.1
	LIPA	NM_001440819.1		c.-1-14239C>T		intron	N/A	NP_001427748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	ENST00000868661.1		c.-1-14239C>T		intron	N/A	ENSP00000538720.1
	LIPA	ENST00000868662.1		c.-1-14239C>T		intron	N/A	ENSP00000538721.1
	LIPA	ENST00000868663.1		c.-1-14239C>T		intron	N/A	ENSP00000538722.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68140 AN: 151840 Hom.: 15914 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68189 AN: 151958 Hom.: 15925 Cov.: 32 AF XY: 0.455 AC XY: 33763 AN XY: 74248

African (AFR) AF: 0.375 AC: 15510 AN: 41404

American (AMR) AF: 0.549 AC: 8388 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3468

East Asian (EAS) AF: 0.814 AC: 4210 AN: 5174

South Asian (SAS) AF: 0.485 AC: 2334 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4869 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29468 AN: 67952

Other (OTH) AF: 0.460 AC: 969 AN: 2106

Alfa AF: 0.439 Hom.: 7858

Bravo AF: 0.457

Asia WGS AF: 0.627 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.75
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7922193; hg19: chr10-91021645;